When a light scattering material, for example a biological tissue or a polymer film containing dispersed colloidal particles, is examined using methods like infrared absorption spectroscopy, information about the material including the concentration of an analyte in the material (solvent, glucose, drug) may be lost due to light scattering by the material. Non-invasive monitoring of patient during a course of treatment, for example monitoring a patient undergoing chemotherapy, monitoring the uptake of topically applied drugs in a patient, or monitoring glucose concentration in a diabetic patient offers many advantages over invasive measurements since non-invasive monitoring could be performed intermittently or continuously by the patient and without the need to withdraw of blood or perform complex chemical tests. Intermittent blood glucose tests, which are widely practiced by diabetic patients, involve pain and discomfort from frequent finger pricking.
There are several electro-chemical methods to determine blood glucose concentration, which require collecting a small blood sample. There are optical approaches for monitoring glucose concentration in patients that do not require collecting biological samples. These optical techniques have primarily focused on measuring glucose concentration by following the changes in the optical properties in the aqueous chamber located between the crystalline lens and cornea. The reason for this is that the biological fluid examined is relatively homogeneous and scattering is rather weak. Examples are: U.S. Pat. No. 3,958,560 that discusses near infra-red (NIR) optical activity in the aqueous humor: U.S. Pat. No. 5,835,215 that discloses absorbance in the aqueous humor; U.S. Pat. Nos. 5,433,197 and 6,152,875 wherein the refractive index of the aqueous humor are discussed.
Blood plasma comprises around 20% of the body's extracellular fluid and is very similar in composition to interstitial fluid except that interstitial fluid primarily contains much less protein, around 2% by volume compared to blood plasma because most of the plasma protein molecules are too large to pass through the capillary walls into the interstitial area. The small amount of protein which does pass through the capillary walls is eventually taken up by the lymph and then ultimately returned to the blood. The relative proportions of plasma proteins can vary in certain diseases and can be a useful diagnostic aid. For example, albumin is among the smallest of the plasma proteins is just small enough to pass through capillary walls. In a healthy patient, this leads to a small amount of albumin in the interstitial fluid. However in patients with kidney disease large amounts of albumin may to leak out through the damaged kidney tubules and may be detected in the interstitial fluid or urine. Blood has a complex composition, and some of the various components include those shown in Table 1.
TABLE 1BloodComponentsReference RangeWater78-78.8g/dlHemoglobin6-18g/dlGlucose40-500mg/dCholesterol80-800mg/dlAlbumin3-5g/dl
Analysis of various plasma components may be made using spectroscopic measurements. The mid- and near-IR spectral ranges are of special importance for spectroscopic identification and analysis using absorption spectroscopy. The mid-IR (λ=2.5μ to 25μ; ω=4000−400 cm−1) is useful for molecular identification; each absorption band in the spectrum of a molecule corresponds to a vibrational transition within the molecule and gives a measure of the frequency at which the vibration occurs.
In materials that have one or more components with different refractive indices, it may be difficult to obtain information about a material or an analyte concentration in the material directly from an absorption spectrum because of light scattering. There is a need to isolate the influence of scattering from absorption coefficients in a variety of materials like human skin which is a highly heterogeneous, multi-layer medium whose optical properties are rather specific to each individual. For other turbid and optically dense materials that exhibit multiple light scattering, such as a polymer having dispersed colloidal particles or a bacterial slime film growing on a surface, the absorption characteristics of these materials and interstitial molecules in the materials can also be obscured by scattering of incident light from the spectrometer. It would be advantageous to characterize optically dense materials using an apparatus and method that can independently determine the scattering and absorption coefficients of the material from light incident on the material.